Intracranial Meningioma

Intracranial meningioma is the most common primary brain tumor in dogs and cats, arising from the arachnoid cap cells of the meninges. These tumors are typically benign, slow-growing, and well-circumscribed, but their location within the calvarium can cause significant neurological deficits due to mass effect, peritumoral edema, and invasion of adjacent structures. In veterinary medicine, meningiomas account for approximately 40-50% of all primary brain tumors in dogs and up to 70% in cats. They are classified histologically into grades I (benign), II (atypical), and III (anaplastic) according to the World Health Organization (WHO) criteria, with the vast majority being grade I. Surgical resection is the mainstay of treatment, often combined with adjunctive therapies such as radiation therapy or chemotherapy, depending on tumor location, resectability, and histologic grade. The goal of surgery is gross total resection (GTR) when feasible, which significantly improves survival times and quality of life.

The exact etiology of intracranial meningiomas in veterinary patients remains largely unknown, but several factors have been implicated. Genetic mutations, particularly in the NF2 gene (encoding merlin/schwannomin), are well-documented in human meningiomas and have been identified in some canine tumors. Chromosomal aberrations, such as monosomy 22 in humans, have also been reported in canine meningiomas. Hormonal influences are suspected, as progesterone and estrogen receptors have been detected in a subset of canine and feline meningiomas, and there is a higher incidence in female cats. Trauma has been proposed as a potential trigger, though evidence is anecdotal. Viral etiologies, such as simian virus 40 (SV40), have been investigated but not confirmed. In dogs, certain breeds (e.g., Golden Retrievers, Boxers, and German Shepherds) show a higher predisposition, suggesting a genetic component. In cats, no strong breed predilection exists, but domestic shorthairs are overrepresented. Chronic inflammation or exposure to environmental carcinogens has not been definitively linked. The tumor arises from arachnoid cap cells, which are embryologically derived from neural crest cells, and their neoplastic transformation leads to the formation of meningiomas.

Intracranial meningiomas are the most common primary brain tumor in both dogs and cats. In dogs, they represent approximately 40-50% of all primary intracranial neoplasms, with a median age of onset around 9-10 years. Brachycephalic breeds, particularly Boxers, Golden Retrievers, and German Shepherds, are overrepresented. Some studies also report a higher incidence in male dogs, though others show no sex predilection. In cats, meningiomas account for up to 70% of primary brain tumors, with a median age of 10-12 years. Domestic shorthair cats are most commonly affected, and there is a slight female predominance. No significant breed predisposition is noted in cats. The tumor can occur in any location within the cranial vault, but common sites include the convexities (parasagittal, falcine), the sphenoid ridge, the olfactory groove, and the caudal fossa (brainstem/cerebellopontine angle). Multiple meningiomas are more frequently seen in cats than in dogs. The incidence of intracranial meningiomas appears to be increasing, possibly due to improved diagnostic imaging (MRI) and increased longevity of pets.

Intracranial meningiomas arise from arachnoid cap cells, which are specialized cells of the leptomeninges. These cells undergo neoplastic transformation, leading to the formation of a well-demarcated, often lobulated mass that is attached to the dura mater. The tumor grows slowly, expanding outward and compressing the underlying brain parenchyma. The pathophysiological consequences are primarily due to mass effect, which increases intracranial pressure (ICP) and causes displacement of brain structures. Peritumoral vasogenic edema is common, resulting from disruption of the blood-brain barrier (BBB) and leakage of fluid into the extracellular space. This edema is mediated by vascular endothelial growth factor (VEGF) and other cytokines. As the tumor enlarges, it can cause venous congestion, further exacerbating edema and ischemia. In some cases, the tumor may invade the overlying calvarium, causing hyperostosis or bone lysis. Seizures are a common clinical sign, likely due to cortical irritation and compression. Neurological deficits (e.g., hemiparesis, proprioceptive deficits) result from compression of specific brain regions, such as the motor cortex or internal capsule. In the caudal fossa, meningiomas can compress the brainstem, leading to cranial nerve deficits, ataxia, and vestibular signs. If untreated, progressive tumor growth leads to herniation syndromes (e.g., transtentorial or foramen magnum herniation), which are life-threatening.

Several factors predispose animals to the development of intracranial meningiomas. Age is a significant risk factor, with older animals (typically >8 years) being more commonly affected. Breed predisposition in dogs includes brachycephalic breeds such as Boxers, Golden Retrievers, and German Shepherds, suggesting a genetic component. In cats, no specific breed is overrepresented, but domestic shorthairs are common. Sex: Some studies report a slight female predominance in cats, while in dogs, the data are conflicting. Hormonal factors: The presence of progesterone and estrogen receptors in some meningiomas suggests a hormonal influence, and there is anecdotal evidence of tumor growth during pregnancy or with exogenous hormone administration. Genetic mutations: Mutations in the NF2 gene, which encodes merlin, are implicated in human meningiomas and have been found in some canine tumors. Other chromosomal abnormalities, such as loss of chromosome 22, have been reported. Environmental factors: Exposure to ionizing radiation is a known risk factor for meningiomas in humans, but this is rarely relevant in veterinary patients. Trauma has been suggested as a potential trigger, but evidence is lacking. Chronic inflammation or infection has not been definitively linked. Overall, the exact predisposing factors remain largely unknown, and most cases are considered spontaneous.

Clinical signs of intracranial meningiomas are variable and depend on the tumor location, size, and rate of growth. Common signs include seizures, which are often the first presenting sign, especially in dogs with forebrain tumors. Seizures may be focal or generalized. Other signs of forebrain involvement include behavioral changes (e.g., aggression, depression, disorientation), circling, head pressing, and visual deficits (e.g., blindness with normal pupillary light reflexes due to optic tract compression). Hemiparesis and proprioceptive deficits may be observed contralateral to the lesion. If the tumor involves the brainstem (caudal fossa), signs include cranial nerve deficits (e.g., facial nerve paralysis, vestibular signs such as head tilt, nystagmus, ataxia), and possibly paresis. In cats, clinical signs are often more insidious and may include lethargy, anorexia, and subtle behavioral changes. As the tumor progresses, signs of increased intracranial pressure (ICP) may develop, including stupor, coma, and papilledema (though papilledema is rarely detected in animals). Neurological examination findings are typically progressive, and the onset may be gradual over weeks to months. In some cases, acute decompensation can occur due to hemorrhage or rapid edema formation.

Differential diagnoses for intracranial meningioma include other primary brain tumors such as glioma (astrocytoma, oligodendroglioma), which are more common in brachycephalic breeds and often have a more infiltrative growth pattern. Choroid plexus tumors (papilloma, carcinoma) are typically located in the ventricles and may cause hydrocephalus. Pituitary tumors (adenoma, adenocarcinoma) are located at the base of the brain and may cause endocrine signs. Metastatic brain tumors (e.g., from mammary carcinoma, melanoma, hemangiosarcoma) are more common in older animals and may be multiple. Inflammatory diseases such as granulomatous meningoencephalomyelitis (GME) can mimic brain tumors on MRI and may present with similar clinical signs. Infectious diseases (e.g., toxoplasmosis, cryptococcosis, ehrlichiosis) can cause focal brain lesions. Vascular events such as cerebrovascular accidents (stroke) can cause acute onset of neurological signs. Congenital anomalies like hydrocephalus or arachnoid cysts may also be considered. Diagnostic imaging (MRI) is essential to differentiate these conditions, but definitive diagnosis requires histopathology. Key features that help rule in meningioma include a well-circumscribed, extra-axial mass with broad-based dural attachment, strong contrast enhancement, and presence of a dural tail sign on MRI. In contrast, gliomas are intra-axial and poorly marginated. Inflammatory lesions often show multifocal or diffuse enhancement and may have a different distribution.

The diagnostic algorithm for suspected intracranial meningioma begins with a thorough history and complete neurological examination to localize the lesion. Baseline blood work (CBC, serum biochemistry, urinalysis) and thoracic radiographs are recommended to rule out systemic disease and metastatic disease. If a brain tumor is suspected, advanced imaging is the next step. Magnetic resonance imaging (MRI) is the modality of choice, providing excellent soft tissue contrast and detailed anatomical information. MRI features of meningioma include a well-defined, extra-axial mass with a broad dural base, isointense to hypointense on T1-weighted images, hyperintense on T2-weighted images, and strong, homogeneous contrast enhancement. A dural tail sign is often present. Computed tomography (CT) can also be used, especially if MRI is unavailable, and may show a hyperattenuating mass with contrast enhancement and associated bone changes. If surgery is planned, a CT scan may be performed for surgical planning, including 3D reconstructions. Cerebrospinal fluid (CSF) analysis may be performed, but it is often non-specific and can be risky if ICP is elevated. CSF findings in meningioma may include mild pleocytosis and elevated protein. Definitive diagnosis requires histopathological examination of a biopsy sample, which can be obtained via surgical resection or stereotactic biopsy. In cases where surgery is not feasible, a presumptive diagnosis can be made based on imaging characteristics, and treatment with radiation therapy or chemotherapy may be initiated.

Laboratory findings in animals with intracranial meningioma are typically non-specific. Complete blood count (CBC) may be within normal limits, though a mild stress leukogram may be present. Serum biochemistry profile is usually unremarkable, but liver enzyme elevations may be seen if the animal has been on long-term anticonvulsant therapy (e.g., phenobarbital). Urinalysis is generally normal. Coagulation panel (PT/aPTT) is recommended prior to surgery to assess bleeding risk, especially if the animal has been on NSAIDs or has concurrent disease. In some cases, inflammatory biomarkers such as C-reactive protein (CRP) may be elevated, but this is not specific. Cerebrospinal fluid (CSF) analysis may show mild to moderate pleocytosis (lymphocytic or mixed) and elevated protein concentration, but these findings are not diagnostic. CSF cytology rarely reveals neoplastic cells in meningioma. If a hormonal influence is suspected, serum progesterone and estrogen levels may be measured, but this is not routinely performed. Overall, laboratory findings are used to rule out other systemic diseases and to assess anesthetic risk, rather than to diagnose meningioma.

Imaging is crucial for the diagnosis and surgical planning of intracranial meningiomas. Magnetic resonance imaging (MRI) is the gold standard. On T1-weighted images, meningiomas typically appear isointense to hypointense relative to normal brain parenchyma. On T2-weighted images, they are often hyperintense, and there may be associated peritumoral edema, which appears as hyperintensity in the white matter. After intravenous administration of gadolinium-based contrast, meningiomas show strong, homogeneous enhancement, and a characteristic dural tail sign (thickening and enhancement of the adjacent dura) is often present. The mass is typically extra-axial, well-circumscribed, and may cause mass effect with midline shift. In some cases, there may be associated calvarial hyperostosis or bone lysis. Computed tomography (CT) is also useful, especially for evaluating bone involvement. On CT, meningiomas appear as hyperattenuating masses that enhance strongly after contrast administration. CT is particularly helpful for surgical planning, as it provides excellent bony detail and allows for 3D reconstructions. Advanced imaging techniques such as magnetic resonance spectroscopy (MRS) and perfusion MRI may provide additional metabolic information but are not routinely used in veterinary practice. In cases where MRI is not available, CT with contrast is a reasonable alternative. Imaging is also used for stereotactic biopsy planning and for radiation therapy planning.

Cytological evaluation of cerebrospinal fluid (CSF) is rarely diagnostic for meningioma, as neoplastic cells are seldom exfoliated. However, CSF analysis may show mild lymphocytic pleocytosis and elevated protein. Fine-needle aspiration of the tumor is not typically performed due to the risk of hemorrhage and brain damage. Definitive diagnosis requires histopathological examination of a biopsy specimen. On gross examination, meningiomas are typically well-circumscribed, firm, and attached to the dura. They may be grayish-white to reddish-brown, depending on vascularity. Histologically, meningiomas are classified into several subtypes, including meningothelial, fibrous, transitional, psammomatous, and angiomatous. The most common subtype in dogs and cats is the meningothelial or transitional type. Histological features include whorl formation, psammoma bodies (calcified concretions), and nuclear atypia. The WHO grading system for meningiomas is based on mitotic count, cellularity, nuclear atypia, and presence of necrosis or brain invasion. Grade I (benign) tumors have a low mitotic index (<4 per 10 high-power fields) and lack atypical features. Grade II (atypical) tumors have increased mitotic activity (4-19 per 10 HPF) or brain invasion. Grade III (anaplastic) tumors have a high mitotic index (>20 per 10 HPF) and marked anaplasia. Immunohistochemistry can be used to confirm the diagnosis, with positive staining for vimentin and often for epithelial membrane antigen (EMA). In cats, meningiomas may be more likely to be multiple and have a more benign behavior.

The primary treatment for intracranial meningioma is surgical resection. The goal is gross total resection (GTR), which is associated with the best prognosis. Surgical approaches depend on the tumor location. For convexity or parasagittal meningiomas, a rostrotentorial craniectomy is performed. The patient is positioned in sternal recumbency with the head elevated. A skin incision is made over the lesion, and the temporalis muscle is reflected. A craniectomy is performed using a pneumatic burr or craniotome, creating a bone flap that can be replaced. The dura is incised, and the tumor is carefully dissected from the underlying brain using microsurgical techniques. The tumor is often well-demarcated and can be removed en bloc. Hemostasis is achieved with bipolar electrocautery and hemostatic agents (e.g., gelatin sponge, oxidized cellulose). The dura is closed with 4-0 or 5-0 absorbable suture (e.g., polydioxanone), and the bone flap is replaced and secured with miniplates or sutures. For olfactory groove meningiomas, a transfrontal approach may be used. For caudal fossa meningiomas, a suboccipital craniectomy is performed. In cats, meningiomas are often more superficial and may be removed with a less invasive approach. If GTR is not possible due to tumor location (e.g., brainstem involvement), a debulking (subtotal resection) is performed, followed by adjunctive radiation therapy. Radiation therapy is also recommended for grade II and III tumors, even after GTR. Chemotherapy (e.g., hydroxyurea, lomustine) may be used for incompletely resected or recurrent tumors, but its efficacy is limited. Postoperative care includes intensive monitoring, seizure control, and management of cerebral edema with corticosteroids (e.g., dexamethasone at 0.1-0.2 mg/kg IV q12h, tapering). Pain management includes opioids (e.g., hydromorphone 0.05-0.1 mg/kg IV q4-6h) and NSAIDs after 24 hours if no contraindications.

The prognosis for intracranial meningioma is generally good with surgical resection. In dogs, median survival times (MST) after surgical resection alone range from 7 to 12 months, with some studies reporting up to 30 months. In cats, the prognosis is better, with MSTs of 20-30 months or longer. Factors associated with a better prognosis include gross total resection, grade I histology, and absence of neurological deficits at presentation. Tumors located in the rostral cerebrum (e.g., olfactory groove) are more amenable to complete resection and have a better prognosis. Conversely, tumors involving the brainstem or those that are incompletely resected have a poorer prognosis. Atypical (grade II) and anaplastic (grade III) meningiomas have a higher recurrence rate and shorter survival times. The addition of radiation therapy after incomplete resection can improve local control and survival. Postoperative complications, such as hemorrhage, infection, or cerebral edema, can negatively impact prognosis. Overall, the 1-year survival rate for dogs with meningioma after surgery is approximately 50-60%, and for cats, it is over 70%. Long-term quality of life is often good, and many animals regain normal function.

Postoperative follow-up is essential to monitor for recurrence and manage complications. Immediately after surgery, patients are hospitalized for 24-72 hours for intensive care, including neurological assessments every 2-4 hours. Pain management is continued for 3-5 days. Skin sutures or staples are removed 10-14 days after surgery. Neurological examinations are repeated at 2, 4, and 8 weeks postoperatively. If the patient is on anticonvulsant therapy, serum drug levels (e.g., phenobarbital) should be monitored and adjusted. Repeat MRI is recommended at 3-6 months postoperatively to assess for residual tumor or recurrence, and then every 6-12 months thereafter. In cases of incomplete resection or high-grade tumors, radiation therapy may be initiated within 2-4 weeks after surgery. Activity restriction is advised for 4-6 weeks to allow for bone healing if a craniectomy was performed. Physical rehabilitation may be beneficial for patients with residual neurological deficits. Long-term monitoring includes regular neurological examinations and imaging as needed. Owners should be educated on signs of tumor recurrence, such as seizures, behavioral changes, or gait abnormalities, and advised to seek immediate veterinary attention if these occur.

Clinical Pearls: 1. Always perform a thorough neurological examination to localize the lesion before imaging. 2. MRI is essential for surgical planning; use T1-weighted post-contrast images to identify the dural tail and tumor margins. 3. For convexity meningiomas, a rostrotentorial craniectomy with a bone flap provides excellent exposure. 4. Use microsurgical techniques and bipolar electrocautery to minimize trauma to surrounding brain tissue. 5. In cats, meningiomas are often more superficial and may be removed with a less invasive approach. 6. Administer corticosteroids (e.g., dexamethasone 0.1-0.2 mg/kg IV) preoperatively to reduce cerebral edema. 7. Control seizures with anticonvulsants (e.g., phenobarbital 2.5-5 mg/kg PO q12h) before and after surgery. 8. Consider radiation therapy for incompletely resected or high-grade tumors. Pitfalls: 1. Avoid entering the tumor capsule, as this can lead to hemorrhage and incomplete resection. 2. Do not compromise the sagittal sinus if the tumor is parasagittal; use careful dissection and hemostasis. 3. Be cautious with brain retraction, as excessive retraction can cause iatrogenic brain injury. 4. Do not close the dura too tightly, as this can increase intracranial pressure. 5. Monitor for postoperative hemorrhage and cerebral edema; have a low threshold for repeat imaging. 6. Do not forget to check coagulation status preoperatively, as bleeding disorders can complicate surgery. 7. Avoid using NSAIDs preoperatively if there is a risk of bleeding. 8. In cats, be aware of the potential for multiple meningiomas; perform a complete MRI of the brain.

Perioperative drug protocols for intracranial meningioma surgery are based on Plumb's Veterinary Drug Handbook. Preoperative: Corticosteroids: Dexamethasone (0.1-0.2 mg/kg IV) or prednisone (0.5-1 mg/kg PO) to reduce cerebral edema. Anticonvulsants: Phenobarbital (2.5-5 mg/kg PO q12h) or levetiracetam (20 mg/kg PO q8h) for seizure control. Prophylactic antibiotics: Cefazolin (22 mg/kg IV) administered 30 minutes before incision and repeated every 90 minutes during surgery. Intraoperative: Mannitol (0.5-1 g/kg IV over 20-30 minutes) may be given to reduce intracranial pressure if needed. Furosemide (0.5-1 mg/kg IV) can be used as an adjunct. Postoperative: Analgesics: Opioids such as hydromorphone (0.05-0.1 mg/kg IV q4-6h) or fentanyl CRI (2-5 mcg/kg/hr) for 24-48 hours. NSAIDs (e.g., carprofen 2.2 mg/kg PO q12h or meloxicam 0.1 mg/kg PO q24h) can be started after 24 hours if no contraindications. Corticosteroids: Continue dexamethasone (0.05-0.1 mg/kg IV/PO q12h) tapering over 1-2 weeks. Anticonvulsants: Continue phenobarbital or levetiracetam as needed. Gastroprotectants: Omeprazole (0.7-1 mg/kg PO q24h) or famotidine (0.5-1 mg/kg IV/PO q12h) to prevent gastric ulcers from corticosteroid use. Antiemetics: Maropitant (1 mg/kg SC q24h) if vomiting occurs. For radiation therapy, protocols may include the use of radiosensitizers, but these are not standard. Chemotherapy agents such as hydroxyurea (50 mg/kg PO q48h) or lomustine (60-90 mg/m² PO q3-4 weeks) may be used for recurrent or high-grade tumors, but their efficacy is variable.

Several studies have evaluated the outcome of surgical resection for intracranial meningiomas in dogs and cats. A landmark study by Heidner et al. (1991) reported a median survival time of 7 months in dogs after surgical resection alone. More recent studies have shown improved outcomes with the use of MRI and microsurgical techniques. For example, a study by Klopp et al. (2005) reported a median survival time of 12 months in dogs with complete resection. In cats, a study by Troxel et al. (2003) reported a median survival time of 20 months after surgery. The role of radiation therapy has been evaluated in several studies. A study by Bley et al. (2005) showed that dogs with incompletely resected meningiomas that received radiation therapy had a median survival time of 16 months, compared to 6 months for those that did not. A more recent study by Keyerleber et al. (2015) reported a median survival time of 18 months for dogs with meningiomas treated with surgery and radiation therapy. The use of chemotherapy has been less well-studied, but a study by Van Meervenne et al. (2014) found that hydroxyurea had some efficacy in dogs with recurrent meningiomas. Consensus guidelines from the ACVS and ECVS recommend surgical resection as the primary treatment for accessible meningiomas, with radiation therapy for incompletely resected or high-grade tumors. The prognosis is generally good, especially in cats, and early diagnosis and treatment are associated with better outcomes.